Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid hormones and their metabolising enzymes have been studied extensively for their potential role in prostate cancer, with more recent interest in the androgen/estrogen inactivating enzyme 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4). Gene expression profiling showed HSD17B4 to be significantly overexpressed in prostate cancer compared to matched-benign epithelium. We therefore hypothesized that altered HSD17B4 expression may contribute to prostate cancer progression via altered hormone balance. In this study, HSD17B4 mRNA and protein expression were assessed by in situ hybridisation (ISH) and immunohistochemistry (IHC), respectively, in tissue arrays of prostate tissue from 172 patients treated by radical prostatectomy. Overexpression of HSD17B4 mRNA and protein was associated with prostate cancer (P<0.0001) and multivariate Cox proportional hazards analysis, adjusted for known prognostic indicators, demonstrated HSD17B4 mRNA and high protein expression were significant independent predictors of poor patient outcome as measured by time until PSA relapse (mRNA: hazards ratio [HR]=1.90, 95% confidence interval [CI]=1.15-3.12; P<0.0001; and protein: HR=2.09, 95% CI=1.31-3.33; P=0.0026). Here we provide strong evidence that both mRNA and protein overexpression of HSD17B4 is not only associated with the presence of prostate cancer, but is also a significant independent predictor of poor patient outcome.
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PMID:HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer. 1910 Mar 8

Androgens are reported to be actively produced in situ in human prostate cancer. These locally produced androgens are also demonstrated to play important role in the pathogenesis and development of human prostate cancer. The status of locally produced androgen inactivation and metabolism, however, remains unclear. Therefore, it is important to examine the status of this in situ androgen metabolism and inactivation in order to improve clinical response to endocrine therapy in the patients diagnosed with prostate cancer. 17beta-hydroxysteroid dehydrogenase type 11 (Pan1b) was demonstrated to display greatest activity with 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol) as substrate in several human androgen metabolizing tissues, suggesting that this enzyme may play important role in androgen metabolism. However, its details including the expression level of Pan1b have not been studied in human prostate cancer. In this study, we evaluated immunolocalization of Pan1b in human prostate cancer specimens obtained from surgery (n=40), and correlated the findings with clinicopathological features of the patients in order to study its clinical significance. Pan1b immunoreactivity was detected in 19 cases (48%) and was significantly associated with cancer of seminal vesicle invasion (P<0.05). Theses data suggest that Pan1b expression could be connected with advanced prostate cancer.
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PMID:17beta-hydroxysteroid dehydrogenase type 11 (Pan1b) expression in human prostate cancer. 1946 52

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the regulation of estrogens and androgens by catalyzing the reduction of 17-ketosteroids or the oxidation of 17beta hydroxysteroids. The enzyme activities associated with the different 17beta-HSD isoforms are widespread in human tissues, not only in classic steroidogenic tissues but also in a large series of peripheral intracrine tissues. Being involved at the end of steroidogenesis, the numerous members of 17beta-HSD family constitute interesting therapeutic targets for controlling the concentration of estrogens and androgens. Thus, inhibitors of reductive 17beta-HSD isoforms are attractive to block the formation of hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian, and endometrium cancers) and androgeno-sensitive pathologies (prostate cancer, benign prostatic hyperplasia, acne, and hirsutism). The inhibitors could be used to block the degradation of estradiol, an attractive strategy for treating osteoporosis and Alzheimer's disease. In addition to their classical use as anti-cancer agents and therapeutic agents, inhibitors of 17beta-HSDs are also useful tools to elucidate the role of these enzymes in particular biological systems. The present review article gives a description of novel inhibitors of 17beta-HSDs that were published in 2003-2006.
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PMID:Advances in development of inhibitors of 17beta hydroxysteroid dehydrogenases. 1960 47

Non-steroidal compounds that inhibit 17beta-hydroxysteroid dehydrogenase isoform 3 (17beta-HSD3), an enzyme catalyzing the final step in testosterone biosynthesis in Leydig cells, are under development for male contraceptive or treatment of androgen dependent diseases including prostate cancer. A series of curcumin analogues with more stable chemical structures were compared to curcumin as inhibitors of 17beta-HSD3 in rat intact Leydig cells as well as rat and human testis microsomes.
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PMID:Curcumin derivatives inhibit testicular 17beta-hydroxysteroid dehydrogenase 3. 2034 54


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